Myosin X regulates neuronal radial migration through interacting with N-cadherin.

Mingming Lai,Huali Yu,Xiaojuan Zhu,Yousra S Malik,Dongdong Zhao,Wencheng Xiong,Xingda Ju,Muhammad A Sheikh,Jun Ma,Ye Guo,Weixiang Guo,Wenqiang Fan

doi:10.3389/fncel.2015.00326

Abstract

Proper brain function depends on correct neuronal migration during development, which is known to be regulated by cytoskeletal dynamics and cell-cell adhesion. Myosin X (Myo10), an uncharacteristic member of the myosin family, is an important regulator of cytoskeleton that modulates cell motilities in many different cellular contexts. We previously reported that Myo10 was required for neuronal migration in the developing cerebral cortex, but the underlying mechanism was still largely unknown. Here, we found that knockdown of Myo10 expression disturbed the adherence of migrating neurons to radial glial fibers through abolishing surface Neuronal cadherin (N-cadherin) expression, thereby impaired neuronal migration in the developmental cortex. Next, we found Myo10 interacted with N-cadherin cellular domain through its FERM domain. Furthermore, we found knockdown of Myo10 disrupted N-cadherin subcellular distribution and led to localization of N-cadherin into Golgi apparatus and endosomal sorting vesicle. Taking together, these results reveal a novel mechanism of Myo10 interacting with N-cadherin and regulating its cell-surface expression, which is required for neuronal adhesion and migration.

Highlights

During neocortical brain development, postmitotic neurons newly generated in the ventricular zone (VZ) and subventricular zone (SVZ) migrate radially toward the pial surface to form the cortical structure (Nadarajah et al, 2001; Gupta et al, 2002; Kriegstein and Noctor, 2004)
We found disturbance of Myo10 in newborn neurons led to impaired radial migration, with an accumulation of enhanced green fluorescent protein (EGFP)+ cells in intermediate zone (IZ) and a decrease of EGFP+ cells in cortical plate (CP) (Figures 1A,B), which is consistent with our previous studies (Yu et al, 2012; Ju et al, 2013)
To characterize more closely the migration defects caused by Myo10 knock-down, we analyzed the neurons detained in the upIZ and loCP regions

Summary

Introduction

Postmitotic neurons newly generated in the ventricular zone (VZ) and subventricular zone (SVZ) migrate radially toward the pial surface to form the cortical structure (Nadarajah et al, 2001; Gupta et al, 2002; Kriegstein and Noctor, 2004). The neurons migrate over a long distance along radial glial fibers from the IZ to arrive close to the top of the cortical plate (CP). The locomotion neurons change their migration mode into the terminal translocation mode (Hatanaka and Murakami, 2002; Nadarajah and Parnavelas, 2002; Tabata and Nakajima, 2003). Myo and N-cadherin regulate neuronal migration the interaction between migrating neurons and radial glial cells (RGCs). The precise molecules that mediate the interaction between migrating neurons and RGCs remain largely unknown

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Discussion

Conclusion